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Background  Hsp90 is an essential molecular chaperone that is also a novel anti-cancer drug target. There is growing interest in developing new drugs that modulate Hsp90 activity.    Methodology/Principal Findings  Using a virtual screening approach, 4-hydroxytamoxifen, the active metabolite of the anti-estrogen drug tamoxifen, was identified as a putative Hsp90 ligand. Surprisingly, while all drugs targeting Hsp90 inhibit the chaperone ATPase activity, it was found experimentally that 4-hydroxytamoxifen and tamoxifen enhance rather than inhibit Hsp90 ATPase.    Conclusions/Significance  Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.

Tamoxifen Enhances the Hsp90 Molecular Chaperone ATPase Activity